22 July 2019 : Laboratory Research
Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling
Yang Gu1ABCDEF, Jin Geng1BCF, Zhuo Xu1CD, Yu Chen1DE, Xi-Wen Zhang1AG*DOI: 10.12659/MSM.915108
Med Sci Monit 2019; 25:5426-5434
Abstract
BACKGROUND: The neutrophil inflammatory protein, lipocalin-2 (NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, the specific role of NGAL in cardiac hypoxia injury is unclear. This study aimed to elucidate the functional role of NGAL in cardiomyocyte hypoxia injury.
MATERIAL AND METHODS: Neonatal rat cardiomyocytes were transfected with adenovirus [(Ad-NGAL] to overexpress human-NGAL and then were exposed to hypoxia for 24 h to establish a hypoxia model. Cell inflammation was detected by RT-PCT and ELISA assay. Cell apoptosis was detected by TUNEL assay. Oxidative stress was also detected by commercial kits.
RESULTS: An increased inflammatory response, apoptosis, and augmented oxidative stress were observed after exposure to hypoxia, while NGAL overexpression in cells increased the expression and release of inflammatory cytokines. NGAL overexpression also increased the number of apoptotic cells and the imbalance of Bax/Bcl-2 protein expression. Moreover, NGAL overexpression increased the levels of reactive oxygen species and oxidase activity, but reduced anti-oxidase activity. Mechanistically, we found that NGAL decreased the expression of integrin β3, but not the expression of integrin avβ3 and avβ5, thus inhibiting the downstream protein AKT. When we used the constitutively activated AKT overexpression adenovirus to activate AKT, the deteriorated phenotype by NGAL was counteracted.
CONCLUSIONS: NGAL can directly affect cardiomyocytes and cause cardiomyocyte deteriorated hypoxia injury through inhibiting integrin β3 signaling.
Keywords: Cell Hypoxia, Integrin beta3, Myocytes, Cardiac, Acute-Phase Proteins, Animals, Newborn, Cardiomegaly, Lipocalin-2, Lipocalins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, bcl-2-Associated X Protein
Editorial
01 March 2023 : Editorial
Editorial: Global Surveillance of Highly Pathogenic Avian Influenza Viruses in Poultry, Wild Birds, and Mammals to Prevent a Human Influenza PandemicDOI: 10.12659/MSM.939968
Med Sci Monit 2023; 29:e939968
SARS-CoV-2/COVID-19
09 February 2023 : Clinical Research
Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...Med Sci Monit 2023; 29:e938892
19 January 2023 : Clinical Research
Determining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical Research
Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...Med Sci Monit 2022; 28:e938926
10 December 2022 : Clinical Research
Retrospective Study to Identify Risk Factors for Severe Disease and Mortality Using the Modified Early Warn...Med Sci Monit 2022; 28:e938647
In Press
27 Mar 2023 : Database Analysis
Relationship Between Physical Activity and Adult Asthma Control Using NHANES 2011-2020 DataMed Sci Monit In Press; DOI: 10.12659/MSM.939350
27 Mar 2023 : Clinical Research
Evaluation of the One-Hour ¹³C-Propionate Breath Test in 49 Patients from a Single Center in Japan to Detec...Med Sci Monit In Press; DOI: 10.12659/MSM.940238
24 Mar 2023 : Database Analysis
Causes of Death Following Gastric Cancer Diagnosis: A Population-Based AnalysisMed Sci Monit In Press; DOI: 10.12659/MSM.939848
22 Mar 2023 : Special report
One Year On: Poland’s Public Health Initiatives and National Response to Millions of Refugees from UkraineMed Sci Monit In Press; DOI: 10.12659/MSM.940223
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952